Hematologic pathology最新文献

The Ph chromosome was the first specific karyotype abnormality associated with a particular neoplastic disease in humans. For many years it was suspected that chromosome abnormalities might cause cancer by alteration of specific genes or their expression. Significant recent developments in our understanding of the molecular consequences of the Ph translocation strengthen that assumption. The Ph translocation generates a hybrid gene consisting of 5' regulatory, promotor, and exon sequences of the bcr gene on chromosome 22 fused to 3' exons and polyadenylation/termination sequences of the ABL proto-oncogene from chromosome 9. It is well established that fusion of bcr and abl genes plays a crucial role in the pathogenesis of CML and ALL. Molecular methods can therefore be used as diagnostic tools to detect the Ph chromosome. Presently, the model of oncogenesis provided by our knowledge of how the abl proto-oncogene becomes activated as a result of the Ph translocation is one of the clearest models of oncogene activation. Despite the progress made, many areas remain to be explored. One important question is, how the hybrid protein is involved in leukemia. Research aimed at investigating the normal function of abl and bcr may be important in efforts to understand their abnormal functioning in leukemia and to increase our understanding of the disease.

Three patients with consumption coagulopathy due to left atrial thrombosis associated with mitral valve disease are described. They had hypofibrinogenemia (0.7-1.7 g/L), mild thrombocytopenia (104-117 x 10(9)/L), and elevated fibrinos/fibrin degradation products (FDP) (20-64 micrograms/ml). Two patients had bleeding symptoms, and one of these also had two episodes of transient ischemic attack. One without bleeding symptoms had three episodes of transient ischemic attack and repeated retinal vein thrombosis. In two patients, preoperative anticoagulation with either heparin or nafamostat mesilate was followed by an increase in plasma fibrinogen level from 0.7 to 5.6 g/L and a decrease in FDP from 64 to 8 micrograms/ml in one patient, and fibrinogen from 1.0 to 2.8 g/L and FDP from 40 to 5 micrograms/mL in another patient. The mitral valve replacement and thrombectomy were performed uneventfully, and their coagulopathy disappeared thereafter. These three patients had a lower platelet count and a shorter platelet survival time than another three patients with mitral valve disease of a similar severity but without coagulopathy. Hemostatic evaluation should be performed in patients suspected of intracardiac thrombosis.

A 69-year-old man with agnogenic myeloid metaplasia was treated with interferon-alpha 2 as part of a Phase II clinical trial. The patient responded to this treatment with a definite improvement in bone marrow histology, demonstrating increased numbers of hematopoietic colonies and partial resorption of the myelofibrosis. Chromosomal analysis on 20 cells suggested the re-emergence of normal hematopoietic progenitor cells: whereas previously, all metaphase spreads demonstrated a deletion in chromosome 20, the patient was now chimeric, with two of 20 cells exhibiting a normal karyotype. Nevertheless, the patient's anemia progressed during interferon therapy, with the development of an immunologically mediated hemolytic disorder. This hemolytic process developed after prolonged treatment with interferon, accelerated during therapy, and resolved following splenectomy and withdrawal of the drug. Initially, screening tests failed to detect the presence of the autoantibody. Similar immunologic processes may have been overlooked in other patients treated with interferon, especially if tests for autoantibodies were obtained early in their course of treatment. This case suggests a therapeutic role for interferon-alpha 2 in the management of the myeloproliferative diseases. It is presented, too, to underscore the immunomodulatory potential of the biologic response modifiers and their capacity to induce immunologic disorders.

A case of Ph1+ chronic myeloid leukemia in blast crisis (CML-BC) is reported, in which the periodic acid Schiff and myeloperoxidase negative blasts displayed high terminal deoxynucleotidyl activity and coexpressed both B- (CD19, CD10, and CD24) and T- (CD7) lymphoid markers. In line with the immunophenotype, DNA analysis revealed a rearranged configuration of both the immunoglobulin and T-cell receptor (beta, gamma, and delta) genes. In spite of this dual B/T phenotype and genotype, the negativity of CyCD3 favors the suggestion that the target of the neoplastic event is an early B cell, with a cross lineage involvement of the putative common recombinase. However, taking into account that a normal counterpart of a biphenotypic B/T ALL has been recognized, it could be hypothesized that the leukemic transformation may have involved an oligopotent B/T lymphoid precursor. This case confirms the lineage heterogeneity of CML-BC and suggests that DNA analyses coupled to extensive immunophenotyping may allow further insight for a more precise recognition of both normal and leukemic ontogenesis.

The prognostic value of the FAB classification, bone marrow histology, Bournemouth score, and chromosome findings was studied in 88 patients with primary myelodysplastic syndromes. The median survival for the whole group of patients was 22 months (RA 61.7 months, RARS 31.6 months, CMML 15.7 months, RAEB 10.3 months, and RAEBt 8.2 months). Chromosomal abnormalities were found in 37 of the 70 patients investigated (52%). Only the differences in survival between patients with complex versus normal karyotype were statistically significant (p = 0.02). The presence of small blastic cells, located away from the endosteal surface (abnormal localization of immature blasts or ALIP) appears to be a major prognostic factor in predicting the duration of survival and progression to ANLL, especially in the FAB subgroups RA and RARS. Median survival for the 22 ALIP- cases with RA/RARS was 65 months, compared with 31 months for the ALIP+ cases (p = 0.0006). Nine ALIP+ patients (53%) developed ANLL in contrast to 3 (13%) of the ALIP- cases (p = 0.008). By redefining ALIP and evaluating the number and characteristics of the accompanying cells, histological subtypes were distinguished correlating largely with the FAB subgroups. Our findings demonstrate the prognostic importance of bone marrow biopsy and quantifying the complexity of bone marrow chromosome changes. It should be helpful in evaluating current attempts to find effective treatment for patients with MDS.

Diffuse large cell and immunoblastic lymphomas are a heterogeneous group of tumors. They differ phenotypically and genotypically, and their clinical course varies in aggressiveness. This study evaluates the prognostic significance of proliferative activity and compares it with immunophenotype, genotype, and clinical data. Proliferative activity was measured by Ki-67 antibody. In 22 cases of diffuse large cell and immunoblastic lymphoma high proliferative activity (greater than 40%) was associated with longer disease-free survival (average 42 months). In contrast, the patients with lymphomas exhibiting low proliferative activity (less than 40%) died shortly after diagnosis (average 8 months). These differences are statistically significant and indicate a need for large-scale prospective studies.

The gene encoding p53 phosphoprotein, originally believed to be an oncogene, recently has been proposed as a candidate antioncogene (tumor-suppressor gene). Abnormalities of the p53 gene expression have been demonstrated in different human malignancies including carcinomas and sarcomas, but little information concerning p53 immunoreactivity in human lymphomas is so far available. In this study immunohistochemical staining for p53-protein was performed on frozen- and paraffin-embedded samples from patients with Hodgkin's (HD) and non-Hodgkin's lymphomas (NHL). No p53 immunoreactivity could be demonstrated in any cell type in nonneoplastic lymphoid samples, including germinal center cells in reactive lymph nodes and cortical thymocytes. On the other hand, a significant proportion of p53+ neoplastic cells was observed in 23 of 31 cases of HD and 17 of 68 cases of NHL. All positive lymphoma cases were diagnosed as high-grade or CD30+ anaplastic NHL. The demonstration of abnormal expression of p53 protein in these diseases can contribute to addressing unresolved issues regarding the origin and pathogenesis of HD and CD30+ anaplastic lymphomas.

Evidence to support the existence of eosinophilic leukemia (EL) as an autonomous eosinophilic proliferation analogous to other myeloproliferative disorders has been somewhat confusing. Partially obscuring the existence of EL as a distinct entity is the proposal that EL merely represents a clinically aggressive form of hypereosinophilic syndrome. This report details the clinical and pathologic findings in a case of EL. The presence of trisomy 8 and trisomy 21; morphologic, cytochemical, and ultrastructural findings of granular abnormalities and nuclear/cytoplasmic dysynchrony; and a clinical course similar to that of other myeloproliferative disorders support the existence of EL as a rare but distinct entity within the spectrum of myeloproliferative diseases.